WASHINGTON -- Some government-funded researchers who tested AIDS drugs on foster children over the past two decades violated federal rules designed to protect vulnerable youths, U.S. investigators have concluded.

Researchers at the Columbia University Medical Center and New York Presbyterian Hospital failed to obtain and evaluate whether they had proper consent, information and safeguards for foster children, said the Department of Health and Human Services' Office of Human Research Protections.

"When some or all of the subjects (e.g., children) are likely to be vulnerable to coercion or undue influence, additional safeguards have been included in the HHS regulations to protect the rights and welfare of these subjects," the federal agency wrote the research hospital.

The researchers' "records demonstrate a failure ... to obtain sufficient information regarding such safeguards with respect to the enrollment of wards of the state or foster children," the agency concluded.

The Associated Press reported May 4 that researchers in New York, Illinois and several other states funded by the National Institutes of Health had tested AIDS drugs on hundreds of foster children since the 1980s, often without providing the children with independent advocates to protect their rights and interests.

Marilyn Castaldi, a spokeswoman for Columbia, said Thursday the facility was still in the process of responding to the investigative findings but "we take seriously our responsibility to protect children or anyone who receives care at our medical center. "

The two research locations said in correspondence with the government that they were "in the process of planning steps specifically to improve protections for children, and particularly foster children."

They told the government they were increasing the resources going to the Institutional Review Boards that monitor the safety of experiments, improving training for researchers and creating a Web-based system to ensure necessary information for patient safety was collected.

The government cited Columbia and Presbyterian in a letter dated May 23 with violating rules in at least four AIDS studies involving foster children, including:

--Failing to "obtain sufficient information regarding the selection of wards of the state and foster children as research subjects."

--Failing to "obtain sufficient information regarding the process for obtaining permission of parents or guardians for wards of the state or foster children."

--Failing to have enough information to ensure "equitable" selection of patients for the studies.

Federal rules require researchers to provide independent advocates to foster children in a narrow class of experiments that pose more than a minimal risk and do not hold the likelihood of improved health for the test patients. Those rules also require the researchers to follow any additional safeguards imposed by state and local authorities.

In New York City and Illinois, where more than 650 foster children combined were enrolled in AIDS drug tests since the late 1980s, the states required researchers to sign agreements promising to provide the advocates for all foster children.

Several research institutions, including Columbia, told AP last month they did not believe they needed to provide the advocates because their experiments held the promise of improved health for the children. Medical ethicists disagreed, saying the foster kids were vulnerable and required the added protection.

Some states said they wouldn't even consider using foster children in such medical testing because of their vulnerabilities.

Foster care agencies and frontline researchers who enrolled foster kids said they did so in an effort to get them cutting-edge drug treatments not available in the marketplace during the AIDS crisis of the early 1990s.

"These studies, which took place in the 1990s, were instrumental in extending lifesaving HIV treatments to children," Castaldi said Thursday.

AP's story prompted a congressional hearing, at which experts testified that the standards for enrolling foster children in medical experiments varied widely across the country. Some lawmakers complained that the foster kids had fewer protections than prisoners.

The Bush administration told Congress it believed the current legal protections for foster children were adequate if followed, but that it did not monitor researchers to ensure that they had complied with the rules.

OHRP's investigation was prompted by a complaint filed last year by the Alliance for Human Research Protection, an advocacy group in New York that raised concerns about a New York Post story documenting AIDS drug testing at a Catholic charity foster home in the city.

The federal agency is withholding a decision on whether Columbia and Presbyterian should have provided the foster children with independent advocates until it receives more information. But it criticized the institutions for not collecting enough information to even make decisions on what regulations it needed to comply with to protect the children.

The investigation "revealed no evidence" that the hospital's review board "considered and made the required findings when reviewing this research involving children," OHRP concluded.

About 15 years ago, as the first wave of AIDS drugs began showing promise for adults, researchers at sites across the country, including Johns Hopkins University and the University of Maryland, began testing the drugs on HIV-infected children -- some of them foster children.

Now, questions have been raised about whether those foster children were adequately protected by law when they became involved in the clinical trials of potentially lifesaving medications. Yesterday, a congressional subcommittee quizzed researchers and ethicists in search of answers.

"Those trials involved both hope and risk," said U.S. Rep. Wally Herger (R-Calif.), who chaired the House Ways and Means subcommittee hearing. "Concerns have been raised about the right balance between hope and risk and who gets to make that critical decision."

Yesterday's inquiry was prompted by an Associated Press investigation published this month which reported that the research -- funded by the National Institutes of Health and conducted in at least seven states -- involved hundreds of foster children, often without providing them with independent medical advocates to oversee their treatment.

Virginia and the District were not listed as participating in the trials.

"The research . . . was most widespread in the 1990s as foster care agencies sought treatments for their HIV-infected children that weren't yet available in the marketplace," the AP reported. Some foster children died during the trials, according to the wire service, but no records were found to indicate that the deaths were directly attributable to the treatments.

The U.S. Office for Human Research Protections, an arm of the Department of Health and Human Services, has undertaken an investigation of the use of foster children in the AIDS trials. And during yesterday's hearing, lawmakers discussed a patchwork of state policies regarding the involvement of foster children in clinical trials. They learned that in trials where institutional review boards determine that child patients will face minimal risk or are expected to draw direct benefit from the research, no independent medical advocate is required to oversee their care.

Such was the case in Maryland, officials said in recent interviews at the University of Maryland School of Medicine in Baltimore and Johns Hopkins Children's Center.

John J. Farley, associate professor of pediatrics at the U-Md. School of Medicine, said federal regulations should be revised to require such advocates. But he noted that they were not required for the AIDS trials done at U-Md. 15 years ago and were not appointed.

He said fewer than a dozen foster children were involved in the U-Md. trials. Some trials involved breakthrough treatments such as AZT used in combination with another drug. Other trials did not involve medications at all. No foster child was involved in placebo-controlled trials, he said, nor did any die as a result of involvement in the trials.

"I join with my colleagues in feeling they weren't exploited and probably a number of those children are alive today because they had access to those medications," Farley said.

In a statement, Johns Hopkins Medicine said advocates were not required in its research. A spokeswoman declined to provide further information about the children involved in trials there, citing confidentiality.

A spokeswoman at the Maryland Department of Human Resources was unable to say how many foster children in the state were involved in the trials. Department spokesman Norris P. West stressed that they must be viewed in the context of the late 1980s and early 1990s, when a million Americans were estimated to be HIV-positive and the cocktails of drugs that now are regularly prescribed to delay the onset of full-blown AIDS were still on the horizon.

"That was a time when we were desperately looking for something that would slow down the rapid pace and spread of AIDS, including among children," West said in an interview.

"Fifteen years later, looking back it might seem: 'What were they thinking? How could they test kids like that?' At the time, there wasn't a moral dilemma. It was watching a child die."

Deborah Weimer, a University of Maryland law professor and director of the college's AIDS legal clinic, said that in those days, she was worried that foster children were being shut out of AIDS trials because of legal impediments in the system that was supposed to be protecting them.

On a similar note, Moira Ann Szilagyi, a pediatrician testifying on behalf of the American Academy of Pediatrics yesterday, said, "While the headlines seem to suggest that children in foster care were somehow singled out as hapless guinea pigs . . . numerous legal barriers exit for children in foster care even to obtain routine health care."

Still, Rep. Fortney "Pete" Stark (D-Calif.) contended that prisoners involved in medical research have advocates to oversee all participation in medical trials. He suggested that future legislation include similar uniform protections for foster children.

"I think we'd sleep a little better at night if we put in a requirement that children have sufficient advocacy," he said.

NIH-funded HIV/AIDS drug trials involving hundreds of HIV-positive foster children in at least seven states "often" did not appoint independent advocates for the children, according to a review of the studies conducted by the Associated Press, the AP/Long Island Newsday reports. The studies tested AIDS-related medication in hundreds of HIV-positive foster children, allowing the children to receive treatment from "world-class" researchers but also exposing them to the risks of research and potentially serious side effects of the trial drugs, according to the AP/Newsday (Solomon, AP/Long Island Newsday, 5/5). The research among foster children was "most widespread" in the 1990s and was conducted in at least seven states, including Illinois, Louisiana, Maryland, New York, North Carolina, Colorado and Texas, according to the AP/San Francisco Chronicle. More than 48 HIV/AIDS-related drug studies involved foster children, most of whom were poor or minority and ranged in age from infants to late teens, according to government records and interviews, the AP/Chronicle reports. In several of the studies, foster child participants reported side effects, including vomiting, rashes and rapid declines in their CD4+ T cell counts, according to the AP/Chronicle (Solomon, AP/San Francisco Chronicle, 5/4). Some children died during the studies, although state or city agencies could not find evidence that any of the children's deaths being caused by the experimental drugs, according to the AP/Newsday.

Recommendations for Advocates
Since 1983, the government has required that researchers and oversight boards appoint independent advocates for foster children enrolled in a certain type of study that involved "greater than minimal risk and lacked the promise of direct benefit," according to the AP/Newsday (AP/Long Island Newsday, 5/5). The advocates must be independent of the foster care agencies, have some understanding of the medical issues involved in the study and "act in the best interests of the child" throughout the research, according to the AP/Chronicle (AP/San Francisco Chronicle, 5/4). However, child advocates were not appointed for "most" of the NIH-funded AIDS-related studies, despite written promises from research institutions that guardians would be assigned, according to the AP/Newsday. Illinois and New York foster agencies required research institutions to sign documents promising to appoint advocates for the children, regardless of the potential risks and benefits of the studies. However, Illinois officials said that none of the nearly 200 Illinois foster children involved in the trials were appointed advocates, and New York officials found records showing that advocates were assigned to only 142 of the 465 children involved in research in that state, according to the AP/Newsday. In addition, some research institutions, including Children's Memorial Hospital in Chicago and Johns Hopkins University in Baltimore, said they did not provide advocates for foster children participating in studies, the AP/Newsday reports. Some states, including Tennessee and Wisconsin, do not allow foster children to participate in clinical trials, and California requires a judge's order to allow their participation, according to the AP/Newsday.

Researchers Say Advocates Not Needed
Many researchers who enrolled foster children in studies through city or state agencies and "frequently" exempted themselves from appointing advocates by concluding that the research would directly benefit the children and involve minimal risk, the AP/Newsday reports. "Our position is that advocates weren't needed," Marilyn Castaldi, spokesperson for Columbia-Presbyterian Medical Center in New York, said. NIH did not directly track whether researchers appointed advocates for the children; instead, the agency relied on medical review boards made up of volunteers at each research site, according to the AP/Newsday. NIH officials estimate that of the 13,878 children enrolled in pediatric AIDS studies funded by the government since the late 1980s, 5% to 10% of them were foster children, according to the AP/Newsday (AP/Long Island Newsday, 5/5).

Reaction
An unnamed spokesperson for the Office for Human Research Protections said that the agency has a "single, open case investigation" against Columbia-Presbyterian Medical Center, according to the Houston Chronicle. However, the spokesperson added, "I can't speak to any other (institution) or what may happen in the future" (Hopper, Houston Chronicle, 5/4). Arthur Caplan, director of the Center for Bioethics at the University of Pennsylvania School of Medicine, said advocates should have been appointed for the children because the researchers "felt the pressure of a medical crisis and knew there was great uncertainty as to how children would react to AIDS medications that were often toxic for adults," according to the AP/Newsday. "It is exactly that set of circumstances that made it absolutely mandatory to get those kids those advocates," Caplan said, adding, "It is inexcusable that they wouldn't have an advocate for each one of those children." Some of the researchers said that advocates were not required because the researchers "protected the children's interest by carefully explaining risks and benefits to state guardians, foster parents and the children themselves," the AP/Newsday reports. "I understand the ethical dilemma surrounding the introduction of foster children into trials," Mark Kline, a pediatric AIDS expert at Baylor College of Medicine, who does not recall appointing advocates for foster children enrolled in his studies, said. He added, "To say as a group that foster children should be excluded from clinical trials would have meant excluding these children from the best available therapies at the time. From an ethical perspective, I never thought that was a stand I could take" (AP/Long Island Newsday, 5/5).

Institute of Medicine Recommendations
An Institute of Medicine study of Institutional Review Boards -- which are responsible for appointing advocates for foster children who are participating in clinical trials -- concluded that the boards "were overworked, were inappropriately dominated by scientists and lacked focus on patient safety," according to the AP/Las Vegas Sun. "As modern IRBs have tended to become larger and to reflect a broader range of scientific expertise, some IRB deliberations have tended to be dominated by the scientific perspective, increasing the potential to marginalize the perspectives of nonscientist members and those who focus on ethics-based concerns," IOM reported in 2002. IOM said a major problem with IRBs is that they have been taking on too many issues without adequate resources, which has forced them to reduce their focus on patient protection, according to the AP/Sun. IOM recommended that IRBs focus more narrowly on patient protections and eliminate tasks such as investigating researchers for potential conflicts of interest, according to the AP/Sun (Solomon, AP/Las Vegas Sun, 5/4).

Article published May 21, 2005Foster children were helped by medical trials
By MARK W. KLINE

SOMETIMES, hindsight is not 20-20.

In a recent editorial, The Blade (Toledoblade.com) criticized researchers who enrolled foster children with HIV in studies of anti-AIDS drugs without appointing an outside advocate for these children.

In particular, The Blade's editorial said: "Exploitation by any other name is exploitation. The hard truth is these children were expendable because they were already sick, had no one to defend their interests, and were available.

Nothing could be further from the truth. We did not single out these children to be the only ones who received treatment. Instead, we included them along with all other children in the same situation in studies of potentially life-saving therapies. There is a great difference.

The decision should also be considered in the context of that era, when children with AIDS died quickly. They died young. I and others who treated them saw them die because available treatments offered only partial, short-lived benefits.

It was a devastating situation that we fought constantly.

Then, beginning in the mid-1990s, increasingly potent medications began to offer hope. After much study, these medications were approved for adults, but because there were no studies in children, they were not approved for children.

Those children whose parents could afford the drugs received them anyway from physicians willing to provide treatment "off-label."
These doctors had to guess at dosages and which medicines offered the least harm to these children.

Clearly, studies were needed to figure out which drugs at which dosages worked best for these children. And time was of the essence.

As studies of these potentially life-saving remedies began in youngsters to define these important parameters, we who treated them had a choice. We could include children in foster care or we could exclude them from the studies.

If we had elected to treat only children in foster care, then perhaps the criticism would be just. That was not the case. Most of the children in clinical trials were not wards of the state, and they and their parents agreed to the treatment.

Would it have been fair to exclude foster children because they lacked parental advocates?

I personally think it would have been wrong and an ethical lapse to do so. They had to be offered the chance for treatment.
It was, at that time, their only hope.

As we learned from the studies, these are potent therapies that can extend the lives of children with HIV.

Should we have appointed advocates for these children? Our legal experts say it was not necessary because the treatments offered potential benefit to this very vulnerable population and they were being put at no more risk than other children in the same situation.

We did not single out foster children for research. We included them in it, if they and their foster parents wanted them to be part.
In this era when there are few youngsters in the United States born with HIV and when those who have the disease receive potent treatments, it is easy to forget the desperate times when nothing we did seemed to work, and children with HIV were dying quickly.
Those memories are fresher for those of us who work in the Third World where HIV is still a rapid death sentence for millions of children who cannot get these treatments.

Do I regret including these foster children in clinical trials?
No. I had to do something to help them, to extend their lives, which were as precious to me and others in my field as were the lives of those children who had parents to push us to provide them with the most potent treatments available.

Dr. Mark Kline is professor of pediatrics at Baylor College of Medicine and director of the Baylor International Pediatric AIDS Initiative.